Studies with rat lung slices indicated that serotonin, but not histamine, is taken up by a mechanism with the characteristics of active transport. The uptake is inhibited by metabolic poisons such as N-ethylmaleimide, iodoacetate, by low temperature (0 degrees C) and by compounds known to block transport of serotonin into neurones and platelets as, for example, desmethylimipramine and the Lilly compound 110140. The uptake is saturable (Km approximately 5 x 10 to the minus 7th power), rapid (t1/2 approximately 5 min) and relatively specific. Tyramine and, to a lesser extent, tryptamine, compete for the uptake, but N-acetylserotonin, 5,6-dihydroxytryptamine, norepinephrine and histamine do not. The labeled serotonin is uniformly distributed into endogenous stores; reserpine was found to release endogenous and labeled serotonin from the slice in equal proportions, i.e. the specific activity of residual serotonin in the slice was unchanged. Since destruction of serotonergic and adrenergic neurones by 6-hydroxydopamine and 5,6-dihydroxytryptamine did not affect uptake, the stores were non-neuronal. As indicated by histological fluorescence studies, serotonin is present in mast cells located exclusively around small blood vessels.